Urticaria is a common skin disorder that is classified according to its chronicity into acute and chronic forms. It may occur spontaneously or on exposure to a physical factor. In the latter case, the urticaria is classified as a physical urticaria. Physical urticaria may be induced by mechanical and applied pressure, exercise, or exposure to cold, heat, sun, water, or vibration. The urticarial lesions are generally thought to be the result of mast cell activation and degranulation, which is supported by the finding of increased levels of serum histamine during some urticarial flares. Passive transfer experiments, whereupon serum from affected donors is transferred into recipients skin followed by physical stimulation with resultant urticaria at the site of challenge, have been positive in some instances. This suggests the presence of an intrinsic factor in serum, such as IgE, which then mediates activation of tissue mast cells. However, the pathogenesis in general remains unclear and a genetic basis for these disorders has not been elucidated. The purpose of this protocol is to investigate the pathogenic mechanisms of physical urticaria and provide further characterization of the various clinical subtypes. Both adult and pediatric patients undergo standard challenge testing to verify their urticaria. Blood samples are obtained for the investigation of molecular, and genetic pathways involved in the disease process. Following the clinical induction of urticarial manifestations, additional blood samples are collected to determine molecular and genetic changes. Skin biopsies may be obtained prior to and following challenge testing that are analyzed for biochemical and histological markers. Patients receive counseling regarding appropriate management of their disease and may be scheduled for a return visit to provide additional samples and for longitudinal analysis of their disease manifestations. Blood and tissue may be stored for future studies. Our first patient was recently enrolled in this study (June 2009) and since then two additional patients have been evaluated. All patients underwent challenge testing based on their history and blood samples have been collected and stored for biochemical, molecular and when applicable, genetic analysis.